@article {542481,
	title = {Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo.},
	journal = {J Immunol},
	volume = {177},
	number = {7},
	year = {2006},
	month = {2006 Oct 1},
	pages = {4376-83},
	abstract = {Naturally occurring CD4+ regulatory T cells (T(R)) that express CD25 and the transcription factor FoxP3 play a key role in immune homeostasis, preventing immune pathological responses to self and foreign Ags. CTLA-4 is expressed by a high percentage of these cells, and is often considered as a marker for T(R) in experimental and clinical analysis. However, it has not yet been proven that CTLA-4 has a direct role in T(R) function. In this study, using a T cell-mediated colitis model, we demonstrate that anti-CTLA-4 mAb treatment inhibits T(R) function in vivo via direct effects on CTLA-4-expressing T(R), and not via hyperactivation of colitogenic effector T cells. Although anti-CTLA-4 mAb treatment completely inhibits T(R) function, it does not reduce T(R) numbers or their homing to the GALT, suggesting the Ab mediates its function by blockade of a signal required for T(R) activity. In contrast to the striking effect of the Ab, CTLA-4-deficient mice can produce functional T(R), suggesting that under some circumstances other immune regulatory mechanisms, including the production of IL-10, are able to compensate for the loss of the CTLA-4-mediated pathway. This study provides direct evidence that CTLA-4 has a specific, nonredundant role in the function of normal T(R). This role has to be taken into account when targeting CTLA-4 for therapeutic purposes, as such a strategy will not only boost effector T cell responses, but might also break T(R)-mediated self-tolerance.},
	keywords = {Animals, Antibodies, Monoclonal, Antigens, CD, Antigens, CD4, Antigens, CD80, Antigens, CD86, Antigens, Differentiation, Colitis, CTLA-4 Antigen, Disease Models, Animal, Flow Cytometry, Intestines, Lymphoid Tissue, Mice, Mice, Inbred BALB C, Mice, Knockout, Receptors, Interleukin-2, T-Lymphocytes, Regulatory},
	issn = {0022-1767},
	author = {Read, Simon and Greenwald, Rebecca and Izcue, Ana and Robinson, Nicholas and Mandelbrot, Didier and Francisco, Loise and Sharpe, Arlene H and Powrie, Fiona}
}
